[Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway].

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

Tailoring the Growth and Morphology of Lithium Peroxide: Nickel Sulfide/Nickel Phosphate Nanotubes with Optimized Electronic Structure for Lithium-Oxygen Batteries.

Heterogeneous crystalline-amorphous structures, with tunable electronic structures and morphology, hold immense promise as catalysts for lithium-oxygen batteries (LOBs). Herein, a nanotube network constructed by crystalline nickel sulfide/amorphous nickel phosphate (NiS/NiPO) heterostructure is prepared on Ni foam through the sulfurization of the precursor generated hydrothermally. Used as cathodes, the NiS/NiPO nanotubes with optimized electronic structure can induce the deposition of the highly porous and interconnected structure of Li2 O2 with rich Li2 O2 -electrolyte interfaces. Abundant active sites can be created on NiS/NiPO through the charge redistribution for the uniform nucleation and growth of Li2 O2 . Moreover, nanotube networks endow cathodes with efficient transport channels and sufficient space for the accommodation of Li2 O2 . A high discharge capacity of 27 003.6 mAh g-1 and a low charge overpotential of 0.58 V at 1000 mAh g-1 can be achieved at 200 mA g-1 . This work provides valuable insight into the unique role of the electronic structure and morphology of catalysts in the formation mechanisms of Li2 O2 and the performances of LOBs.

Z-DNA/RNA Binding Protein 1 Senses Mitochondrial DNA to Induce Receptor-Interacting Protein Kinase-3/Mixed Lineage Kinase Domain-Like-Driven Necroptosis in Developmental Sevoflurane Neurotoxicity.

Developmental sevoflurane exposure leads to widespread neuronal cell death known as sevoflurane-induced neurotoxicity (SIN). Receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL)-driven necroptosis plays an important role in cell fate. Previous research has shown that inhibition of RIPK1 activity alone did not attenuate SIN. Since RIPK3/MLKL signaling could also be activated by Z-DNA/RNA binding protein 1 (ZBP1), the present study was designed to investigate whether ZBP1-mediated and RIPK3/MLKL-driven necroptosis is involved in SIN through in vitro and in vivo experiments. We found that sevoflurane priming triggers neuronal cell death and LDH release in a time-dependent manner. The expression levels of RIPK1, RIPK3, ZBP1 and membrane phosphorylated MLKL were also dramatically enhanced in SIN. Intriguingly, knockdown of RIPK3, but not RIPK1, abolished MLKL-mediated neuronal necroptosis in SIN. Additionally, inhibition of RIPK3-mediated necroptosis with GSK'872, rather than inhibition of apoptosis with zVAD, significantly ameliorated SIN. Further investigation showed that sevoflurane treatment causes mitochondrial DNA (mtDNA) release into the cytosol. Accordingly, ZBP1 senses cytosolic mtDNA and consequently activates RIPK3/MLKL signaling. This conclusion was reinforced by the evidence that knockdown of ZBP1 or depleting mtDNA with ethidium bromide remarkably improved SIN. Finally, the administration of the RIPK3 inhibitor GSK'872 relieved sevoflurane-induced spatial and emotional disorders without influence on locomotor activity. Altogether, these results illustrate that ZBP1 senses cytosolic mtDNA to induce RIPK3/MLKL-driven necroptosis in SIN. Elucidating the role of necroptosis in SIN will provide new insights into understanding the mechanism of anesthetic exposure in the developing brain.

[Characteristics and Impact Factors of Number Concentration of Primary Biological Aerosol Particles in Beijing].

Primary biological aerosol particles (PBAP) are an important part of ambient aerosols. Both living and dead organisms not only influence human health and air quality but also play important roles in regulating certain atmospheric processes and affect the hydrological cycle and climate change. In this study, flow cytometry (FCM) was utilized in combination with the simultaneous use of permeant (SYBR Green I) and impermeant (propidium iodide, PI) nucleic acid fluorescent staining to detect and quantify the viable and dead airborne biological particles. At the same time, based on this method, the dead/viable PBAP in a Beijing urban area was detected and quantified. Moreover, the influence of environmental factors on the concentrations of primary biological aerosol particles was illuminated. The results showed that the media number concentration of dead and alive PBAP in the Beijing urban area during summer (1.03×106 m-3 and 7.43×105 m-3, respectively) were higher than those during winter (7.34×105 m-3and 6.18×105 m-3, respectively). Statistical analysis showed that there was no significant correlation between PBAP number concentration and environmental factors, i.e., meteorological conditions and air quality, showing a weak positive correlation with temperature and humidity and weak negative correlations with O3, maximum wind speed, and sunshine duration. The number concentration of PBAP was weakly correlated with the mass concentration of PM2.5 but positively correlated with that of coarse particulate matter (PM2.5-10). Both stable weather and dust transport could increase the number concentration of PBAP in Beijing.

miR-322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4.

AIMS: Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR-322, and we have previously demonstrated that miR-322 was involved in high glucose-induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR-322 that disrupts neurulation by ameliorating cell apoptosis. METHODS: All-trans-retinoic acid (ATRA)-induced mouse model was utilized to study NTDs. RNA pull-down and dual-luciferase reporter assays were used to confirm the interaction between NOX4 and miR-322. In mouse neural stem cells and whole-embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR-322 and NOX4 on neuroepithelium apoptosis in NTD formation. RESULTS: NOX4, as a novel target of miR-322, was upregulated in ATRA-induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR-322; still further, NOX4-triggered apoptosis was also suppressed by miR-322. Moreover, in whole-embryo culture, injection of the miR-322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4. CONCLUSION: miR-322/NOX4 plays a crucial role in apoptosis-induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs.

STAT3 signaling statuses determine the fate of resveratrol-treated anaplastic thyroid cancer cells.

BACKGROUNDS: Anaplastic thyroid cancer/ATC is highly lethal malignancy without reliable chemotherapeutic drug. Resveratrol possesses anti-ATC activities but encounters resistance in some cases due to certain unknown reason(s). OBJECTIVE: Because signal transducer and activator of transcription/STAT3 signaling is critical for ATC cell survival and the main molecular target of resveratrol, its roles in determining the fates of resveratrol-treated ATC cells were investigated here. METHODS: Human THJ-11T, THJ-16 and THJ-21T ATC cell lines were treated by 100 µM resveratrol and their growth, statuses of STAT3 signaling and STAT3-related gene expression were examined. The relevance of STAT3 activation with resveratrol resistance was elucidated using STAT selective inhibitor AG490. Leukemia inhibitory factor/LIF expression and phosphorylated-STAT3/p-STAT3 nuclear translocation in ATC tissues were immunohistochemically analyzed. RESULTS: Resveratrol inhibited proliferation, p-STAT3 nuclear translocation as well as LIF and STAT3 expression of THJ-16T and THJ-21T but not THJ-21T cells which showed LIF upregulation and more frequent p-STAT3 nuclear translocation. AG490 significantly prevent p-STAT3 nuclear translocation, and reversed the resveratrol tolerance of THJ-11T cells. Immonohistochemical staining revealed 14.3% (4/28) of LIF and 3.6% (1/28) of p-STAT3 detection in noncancerous ATC-surrounding tissues, which increased to 89.5% (17/19) and 52.6% (10/19) respectively among ATC specimens. The correlative analysis indicated the relevance of LIF expression and STAT3 activation (r= 0.825; P< 0.01). CONCLUSIONS: The status of STAT3 activation and LIF expression are closely correlated with the therapeutic effect of resveratrol on ATCs. Frequent LIF upregulation and STAT3 activation are the unfavorable factors of ATCs and the potential targets of anti-ATC therapy.

Core-shell anatase anode materials for sodium-ion batteries: the impact of oxygen vacancies and nitrogen-doped carbon coating.

In this work, the impact of oxygen vacancies and nitrogen-doped carbon coating on the sodium-ion storage properties of anatase TiO2 has been demonstrated. Oxygen vacancies and nitrogen-doped carbon coating were introduced simultaneously by the calcination of core-shell structured TiO2 spheres in a reducing atmosphere. Compared to the anatase TiO2 with and without oxygen vacancies, TiO2-x@NC exhibits much better electrochemical performance in the storage of sodium ions. A high reversible capacity of 245.6 mA h g-1 is maintained at 0.1 A g-1 after 200 cycles, and a high specific capacity of 155.6 mA h g-1 is achieved at a high rate of 5.0 A g-1. The significantly improved electrochemical performance of the core-shell structured anatase TiO2 spheres is attributed to the synergistic effect of the oxygen vacancies in the anatase lattice and surface nitrogen-doped carbon coating. This work provides an efficient strategy for improving the electrochemical performance of metal-oxide-based electrode materials for sodium-ion batteries.

Neuron-Inspired Design of High-Performance Electrode Materials for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) are generally considered as promising cheap alternatives of lithium-ion batteries for stationary renewable energy storage and have received increasing attention in recent years. The exploration of anode materials with efficient electron transportation is essential for improving the performance of SIBs. Inspired by the signal transfer mode of a neuron, we designed a composite by stringing MoS2 nanoflower (soma) with multiwall carbon nanotubes (MWCNTs) (axons). High-resolution TEM observation reveals a lattice matching growth mechanism of MoS2 nanosheets on the interface of MWCNTs and the lattice expansion of the (002) plane of MoS2. The lattice matching among the MoS2 nanosheet and MWCNT could facilitate electron transfer and structure maintenance upon cycling. The expanded distance of the (002) plane of MoS2 would also promote the sodium-ion intercalation/deintercalation kinetics of the composite. Benefiting from the structural features, when used as an anode material for SIBs, the composite exhibits excellent electrochemical performance, including high specific capacity, excellent cycle stability, and superior rate capabilities. A stable capacity of 527.7 mAh g-1 can be achieved after 110 cycles at a current density of 100 mA g-1. The neuron-inspired design proposed is a promising and efficient strategy for the development of electrode materials for SIBs with high mass transport kinetics and structural stability.

Rubber-based carbon electrode materials derived from dumped tires for efficient sodium-ion storage.

The development of sustainable and low cost electrode materials for sodium-ion batteries has attracted considerable attention. In this work, a carbon composite material decorated with in situ generated ZnS nanoparticles has been prepared via a simple pyrolysis of the rubber powder from dumped tires. Upon being used as an anode material for sodium-ion batteries, the carbon composite shows a high reversible capacity and rate capability. A capacity as high as 267 mA h g-1 is still retained after 100 cycles at a current density of 50 mA g-1. The well dispersed ZnS nanoparticles in carbon significantly enhance the electrochemical performance. The carbon composites derived from the rubber powder are proposed as promising electrode materials for low-cost, large-scale energy storage devices. This work provides a new and effective method for the reuse of dumped tires, contributing to the recycling of valuable waste resources.

[Analysis of Different Particle Sizes, Pollution Characteristics, and Sources of Atmospheric Aerosols During the Spring Dust Period in Beijing].

To understand the evolution of the physical and chemical properties of dust aerosols in the atmosphere, the concentrations and chemical compositions of differently sized particles were continuously observed and analyzed using an ion chromatograph and carbonaceous analyzer during the outbreak of dust in May 2017 in Beijing. The concentrations of total suspended particulate (TSP), water-soluble organic carbon (WSOC), elemental carbon (EC), OC, and water-soluble inorganic ions were (2237.59±681.49), (29.90±18.05), (1.46±3.05), (67.35±29.07), and (136.75±46.38) µg·m-3 during the dust period, respectively, and significantly exceeded that of the non-dust period, except for EC. The Na+, NH4+, K+, Mg2+, Ca2+, Cl-, NO3-, SO42-, and WSOC concentrations during the dust storm period were 11.55, 3.00, 14.88, 14.89, 9.40, 4.60, 2.40, 3.91, and 1.83 times higher than that during the non-dust period. The growth of crustal ions, such as Ca2+ and K+, was notably the largest and NH4+ and NO3- were minimal. The size distribution indicates that crustal ions primarily occur in the coarse mode during the whole sampling campaign. The SO42- and NO3- ions are slightly bimodal during the dust storm, with a dominant peak in the coarse mode at 4.7-5.8 µm and a very minor peak in the fine mode with a size range of 0.43-0.65 µm. During the non-dust period, SO42- is the dominant mode in the fine mode, while NO3- changes little compared with that during the dust period, which indicates that heterogeneous reaction with crustal ions is the main formation mechanism of NO3- in the coarse mode. A significant positive correlation was observed between SO42- and the sum of crustal ions during the dust period, indicating that the source of SO42- during the dust period is remote transmission of the dust storm. During the non-dust period, the positive correlation of SO42- with NH4+ indicates that secondary formation is the main source of SO42-. Based on correlation analysis of NO3- with crustal ions and NH4+, both remote transmission and secondary formation are the sources of NO3- during the dust storm and heterogeneous reactions are predominant during the non-dust period.

Incorporation of heterostructured Sn/SnO nanoparticles in crumpled nitrogen-doped graphene nanosheets for application as anodes in lithium-ion batteries.

Sn/SnO nanoparticles are incorporated in crumpled nitrogen-doped graphene nanosheets by a simple melting diffusion method. The resulting composite exhibits large specific capacity, excellent cycling stability and high rate capability as an anode for lithium-ion batteries.